It is generally accepted that Okazaki pieces, polydeoxyribonucleotide chains of about 500-1000 nucleotides in length, are intermediates in the synthesis of the high molecular weight chromosomal DNA. The mechanism of synthesis of Okazaki pieces, however, especially their initiation, is still little understood. Recent results from our laboratory show that most of the polymerization of nucleotides in HeLa cells occurs at the oligonucleotide level (Jering and Werner, 1976). Together with the exponential size distribution of nascent DNA chains (Kuebbing et. al., 1976) these results suggest that longer chains arise primarily by ligation of oligonucleotides with little further incorporation of mononucleotides. In addition, we found that most nascent DNA chains from HeLa cells that are deprived of thymidine prior to pulse-labeling with 3H-thymidine carry a TMP residue at their 5'-ends while chains from steady-state cells seem to carry all four deoxyribonucleotides with equal frequency. Using these results as a starting point we propose to study the mechanism of DNA chain initiation and elongation at the replication fork.